tbuckley/cabot-search huggingface dataset:
DIPG-42. Diffuse midline gliomas, H3K27-altered as an interdisciplinary challenge
Authors: Gertrud Kammler, Friederike Fritzsche, Uwe Kordes, Ulrich Schüller, Manfred Westphal
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Diffuse midline gliomas represent a particular challenge in treatment. DIPG behave like highly malignant glioma with extremely poor prognosis due to location and inoperability. Molecular genetic studies, complementary to classical histopathology, have found an entity for midline gliomas, newly described ten years ago and entered the WHO classification in 2016. This group of childhood tumor with DMG’s, H3K27-altered will be demonstrated in the following with 14 case reports from our clinic. METHODS: Clinical data of four patients with tectum/thalamic gliomas, six with diffuse intrinsic brainstem glioma, two with cerebellar, one with suprasellar, one with spinal glioma were retrospectively studied. MRI data, volume increase, contrast behavior was also analyzed. Tumor tissue was obtained by various surgical procedures and diagnostic workup included histopathology as well as genetics and epigenetics. RESULTS: 14 pediatric patients were treated from 2012 to 2021, median age 7,5 years. Leading symptoms were hydrocephalus, movement disorders, cranial nerve disorders. Four patients (29%) were partially resected, two (14%) received extended biopsy, seven (50%) were (stereo tactically) biopsied, one diagnosed by liquid biopsy (7%). Histological results revealed the presence of GBM in four cases (29 %). Subsequent methylome analyses confirmed that the tumors belonged to the group of diffuse midline gliomas, H3K27-altered. The other ten tumors (71%) were primarily assigned to this H3K27 group. CONCLUSION: The pediatric tumors of the brainstem, the further midline structures, including intraspinal manifestation show different MRI findings, histology, and clinical course. Complementary molecular genetic diagnosis is essential and a meaningful addition to the histological assignment. It is considered proven that the exclusivity of H3K27 – altered tumors of children and adolescents differs from that of IDH mutated gliomas and glioblastomas by their localization of hemispheric processes. Possible therapeutic approaches using targeted therapy require understanding of these oncological mechanisms.
Effect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial
Authors: Robert H Shaw, Xinxue Liu, Arabella S V Stuart, Melanie Greenland, Parvinder K Aley, Nick J Andrews, J Claire Cameron, Sue Charlton, Elizabeth A Clutterbuck, Andrea M Collins, Wanwisa Dejnirattisai, Tanya Dinesh, Saul N Faust, Daniela M Ferreira, Adam Finn, Christopher A Green, Bassam Hallis, Paul T Heath, Helen Hill, Teresa Lambe, Rajeka Lazarus, Vincenzo Libri, Fei Long, Yama F Mujadidi, Emma L Plested, Ella R Morey, Samuel Provstgaard-Morys, Maheshi N Ramasamy, Mary Ramsay, Robert C Read, Hannah Robinson, Gavin R Screaton, Nisha Singh, David P J Turner, Paul J Turner, Iason Vichos, Laura L Walker, Rachel White, Jonathan S Nguyen-Van-Tam, Matthew D Snape
Journal: The Lancet Respiratory Medicine (2022)
Author correction to ‘Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents’ [Acta Pharmaceutica Sinica B 9 (2019) 335–350]
Authors: Jiabing Wang, Lili Huang, Chanchan Chen, Ge Li, Jingwen Xie, Mengya Shen, Qian Chen, Wulan Li, Wenfei He, Peihong Qiu, Jianzhang Wu
Journal: Acta Pharmaceutica Sinica B (2022)

[This corrects the article DOI: 10.1016/j.apsb.2019.01.003.].
Neoadjuvant radiation case volume and associated with margin-negative resection rates in patients with pancreatic cancer.
Authors: Samih Z Thalji, William A. Hall, Beth Erickson, Mandana Kamgar, Ben George, Kathleen K. Christians, Callisia Clarke, Saryn Doucette, James Miller, Bryan Hunt, Tamara Giorgadze, Douglas B. Evans, Susan Tsai
Journal: Journal of Clinical Oncology (2022)

e16281 Background: High surgical case volume (SCV) is associated with improved outcomes. Whether radiation case volume (RCV) is associated with outcomes is unknown, but of potentially increased importance given the recent results of the PREOPANC trial. We examined the impact of RCV on pathologic outcomes among patients (pts) with pancreatic cancer (PC) receiving neoadjuvant therapy (NAT). Methods: Pts with PC who received any NAT between 2009-2018 were identified from the National Cancer Database. Institutions were defined by SCV (low: &lt; 9, medium:9-35, high:≥36 pts/year) and by RCV (nil:none, low:1-6, high:≥7 pts/year). Pathologic outcomes were node (N0/N1) and margin (R0/R1) status. Results: In total, 10,893 pts received NAT at 890 institutions; 3,522 (32%) received radiation at 562 (63%) institutions. Among all 10,893 pts, 2,896 (26%) were treated at low-SCV, 5,421 (50%) at medium-SCV, and 2,576 (24%) at high-SCV institutions. Among all 10,893 pts, 904 (8%) were treated at nil-RCV institutions, 7,736 (71%) at low-RCV, and 2,253 (21%) at high-RCV institutions. N0 resections were accomplished in 1,210 (54%) of 2,253 pts at high-RCV institutions, 3,732 (48%) of 7,736 at low-RCV, and 339 (38%) of 904 at nil-RCV institutions ( p values &lt; 0.001). Similarly, R0 margins were achieved in 1,979 (88%) of 2,253 pts at high-RCV, 6,380 (82%) of 7,736 at low-RCV, and 671 (74%) of 904 at nil-RCV institutions ( p values &lt; 0.001). Among 3,522 pts that received radiation, N0 resections were not different by RCV: 769 (62%) of 1,241 at high-RCV institutions and 1,461 (64%) of 2,281 at low-RCV institutions ( p= 0.22). Pts treated with radiation at high-RCV institutions had higher proportions of R0 margins: 1,120 (90%) of 1,241 at high-RCV and 1,931 (85%) of 2,281 at low-RCV institutions ( p&lt; 0.001). High-RCV and low-RCV institutions were each associated with N0 resections (Table) and were not different from each other ( p= 0.33). High-RCV and low-RCV institutions were each associated with R0 margins, however high-RCV was more strongly associated than low-RCV ( p&lt; 0.001). Conclusions: Pts at high-RCV facilities had greater odds of R0 margins independent of surgical case volume. As radiation techniques evolve, the value of high-RCV experience is likely to become increasingly important.[Table: see text]
Survival after radical prostatectomy vs. radiation therapy in clinical node-positive prostate cancer
Authors: F. Chierigo, C. Würnschimmel, R.S. Flammia, B. Horlemann, G. Sorce, B. Hoeh, Z. Tian, F. Saad, M. Graefen, M. Gallucci, A. Briganti, F. Montorsi, F.K.H. Chun, S.F. Shariat, G. Mantica, M. Borghesi, S. Nazareno, C. Terrone, P.I. Karakiewicz
Journal: European Urology (2022)
Institutional review of African American (AA) patients with metastatic triple-negative breast cancer.
Authors: Nikitha Vobugari, Ami Chitalia
Journal: Journal of Clinical Oncology (2022)

e13059 Background: Atezolizumab+ Abraxane (Ate+Abx) was approved as 1st line treatment in metastatic TNBC based on IMPASSION (IM) 130 trial and was subsequently withdrawn per IM131 trial. Treatment of mTNBC remains challenging. Pembrolizumab with chemotherapy received accelerated approval based on Keynote-355. Poor outcomes among AA patients (pts) are linked to biological differences, BRCA1/2 mutations, obesity, and socioeconomic barriers. In TNBC clinical trials, AA pts continue to be underrepresented, e.g., 5.8% (26) in IM130 and 4.9% (21) in IM131. Our cancer center sees over 300 new BC pts a year, and at least 50% identify as AA. Here we examine our institutional experience. Methods: IRB-approved retrospective database search was conducted between 01/01/2019- 04/16/2021 to identify 11 pts treated with Ate+Abx for mTNBC at Medstar Washington Hospital Center, DC. Demographic variables manually extracted were age, BMI, insurance type and outcomes. Results: 10/11 (91%) pts were AA with lines of therapy ranging 1-6. 20% (2/10) showed partial response (PR) on 3-month (M) interval imaging per the RECIST 1.1 scoring. PD occurred in 6/10 (60%) of pts, although PD-L1 was positive in 90% (9/10) pts. Time to progression (TTP) was 1-7 M (median 3M) compared to TTP of 5.59 to 7.46M (median 7.16M) for all races in the IM130 study. Autoimmune colitis, peripheral neuropathy, and fatigue were notable adverse effects (AEs). 2/10 (20%) pts discontinued treatment due to AEs. Colitis and neuropathy in IM130 were &lt;1%. Mean age at drug initiation was 52.2 vs. 55 years in IM130, indicating earlier onset of mTNBC in the AA population. Conclusions: Trends of higher PD and earlier TTP were noted in our AA pts. Young age at metastasis, high number of previous lines of therapy, high number of metastatic sites, and obesity were noted amongst our AA mTNBC pts. Positive PD-L1, BRCA mutations, metastatic sites, BMI, or insurance type did not correlate with outcomes. Pts with PR vs. PD were not different in terms of insurance, metastasis sites, and BMI. Differences in AEs are noted; however, the small pt population size and lack of a control group are limitations. While the FDA has withdrawn Ate from trials for mTNBC, this study suggests a need for more AA pts to be included in clinical trials for TNBC. Lack of health care access, insufficient education, inadequate recruitment, and distrust of the medical system are contributing factors that require continued efforts.[Table: see text]
MODL-27. An organotypic brain slice culture platform as a novel pre-clinical model for diffuse intrinsic pontine glioma and diffuse midline glioma
Authors: Breanna Mann, Xiaopei Zhang, Noah Bell, Adebimpe Adefolaju, Rajaneekar Dasari, Alain Valdivia, Andrew Buckley, Carolyn Quinsey, Shawn Hingtgen, Andrew Satterlee
Journal: Neuro-Oncology (2022)

Abstract High-grade pediatric brain tumors (PBTs) such as diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG) are devastating diseases with a median survival of just 11 months. Little progress has been made in identifying effective treatments due to the lack of effective pre-clinical models to accurately assess drug sensitivity. Historically, models of DIPG and DMG have been limited due to the low availability of surgical biopsies and small patient populations. Existing in vitro models are often unable to recapitulate growth and migration patterns seen in patients, while in vivo work is costly, time intensive, and many biopsies fail to establish in mice. We have developed an ex vivo organotypic brain slice culture (OBSC) platform to model DIPG and DMG. Through our partnership with the Ian’s Friends Foundation and Children’s Healthcare of Atlanta Biobank, we have seeded, grown, and treated several low-passage patient-derived PBT lines such as DIPG and DMG. Additionally, we can assess treatment response to a variety of agents used in clinical patient care. Viability assays revealed differences in the sensitivity of cell lines to individual agents, indicating that OBSCs have the potential to capture minute differences in efficacy between cell lines and drugs. When we assessed combination treatments, we found low doses of radiation with low doses of temozolomide were synergistic, but using higher doses of radiation was antagonistic, suggesting the OBSC platform has the potential to guide dosing strategies to maximize therapeutic synergy. Overall, these results suggest that OBSC PBT models have the potential to effectively model PBTs, including DIPG and DMG, to accelerate preclinical evaluation of therapeutics and guide drug development towards more effective treatment strategies.
PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer
Authors: Andrea Cercek, Melissa Lumish, Jenna Sinopoli, Jill Weiss, Jinru Shia, Michelle Lamendola-Essel, Imane H. El Dika, Neil Segal, Marina Shcherba, Ryan Sugarman, Zsofia Stadler, Rona Yaeger, J. Joshua Smith, Benoit Rousseau, Guillem Argiles, Miteshkumar Patel, Avni Desai, Leonard B. Saltz, Maria Widmar, Krishna Iyer, Janie Zhang, Nicole Gianino, Christopher Crane, Paul B. Romesser, Emmanouil P. Pappou, Philip Paty, Julio Garcia-Aguilar, Mithat Gonen, Marc Gollub, Martin R. Weiser, Kurt A. Schalper, Luis A. Diaz
Journal: New England Journal of Medicine (2022)

Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair-deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair-deficient, locally advanced rectal cancer.
Pancreatic Adenocarcinoma: Emerging Systemic Therapy Options
Authors: Margaret A. Tempero
Journal: Journal of the National Comprehensive Cancer Network (2022)

Although we are “winning the war against cancer,” pancreatic malignancies are expected to be the most common cause of cancer-related death by 2040. Several systemic therapies, such as oxaliplatin + irinotecan/fluorouracil/leucovorin (FOLFIRINOX) and gemcitabine + nab-paclitaxel, have shown activity in the adjuvant and neoadjuvant settings. The current NCCN Guidelines reflect the most up-to-date, evidence-based data relating to the evaluation and management of pancreatic adenocarcinoma. They were recently updated to recommend germline testing for any patient with pancreatic cancer and molecular analysis of any metastatic pancreatic tumor.
Perioperative and functional outcomes after kidney transplantation from uncontrolled donors after circulatory death vs. expanded-criteria donors after brain death vs. standard-criteria donors: Toward an evidence-based refinement of allocation strategies
Authors: R. Campi, A. Pecoraro, F. Sessa, P. Barzaghi, A. Rivetti, R. Nicoletti, M.L. Gallo, F. Corti, S. Morselli, P. Spatafora, M. Gacci, S. Giancane, A. Sebastianelli, L. Cirami, A. Peris, G. Vignolini, S. Serni, V. Li Marzi
Journal: European Urology (2022)
Single cell profile of tumor and immune cells in primary triple-negative breast cancer and different sites in the axillary lymph nodes.
Authors: Ning Liao, Cheukfai Li, Li Cao, Yanhua Chen, Chongyang Ren, Xiaoqing Chen, Hsiaopei Mok, Ling-Zhu Wen, Kai Li, Yulei Wang, Yuchen Zhang, Yingzi Li, Jiaoyi Lv, Fangrong Cao, Yuting Luo, Hongrui Li, Wendy Wu, Charles M. Balch, Armando E. Giuliano
Journal: Journal of Clinical Oncology (2022)

e12570 Background: Little is known about the host-tumor interaction in the lymph node basin at a single cell level. This study examines single cell sequences in breast cancer nodal metastasis of a patient with triple negative breast cancer. Methods: The primary breast tumor, sentinel lymph node, an adjacent lymph node with metastatic involvement and a clinically normal-appearing lymph node were collected during operation. Single-cell sequencing was performed on all specimens. Results: 14,016 cells were clustered as 6 cell populations. Cancer cells demonstrated the molecular characteristics of TNBC basal B subtype and highly expressed genes in the MAPK signaling cascade. Tumor associated macrophages regulated antigen processing and presentation and other immune-related pathways to promote tumor invasion. CD8+ and CD4+ T lymphocytes concentrated more in sentinel lymph node and mainly stratified as two transcriptional states. Conclusions: The first single cell report investigates the host-tumor interaction in the lymph node basin of triple-negative breast cancer. Single-cell sequencing analysis suggested that the sentinel lymph node was the initial meeting site of tumor infiltration and immune response, where partial T lymphocytes perform anti-tumor activity while other T cells exhibit an exhaustion state. We proposed a molecular explanation to the well-established clinical principle that the 5-year and 10-year survival outcomes were noninferior between sentinel lymph node dissection (SLND) and axillary lymph node dissection (ALND).
Efficacy of afatinib in patients with advanced/metastatic solid tumors harboring <i>NRG1</i> gene fusions: A novel, prospective real-world outcomes study based on single-patient protocol data.
Authors: Stephen V. Liu, Lori Ann E. Minasi, Matthias Herpers, Claas Frohn
Journal: Journal of Clinical Oncology (2022)

TPS3180 Background: Oncogenic neuregulin 1 ( NRG1) gene fusions occur in ̃0.2% of solid tumors overall and in up to 31% of cases of invasive mucinous lung adenocarcinoma [Laskin et al. Ann Oncol. 2020;31(12):1693–1703; Cadranel et al. Oncologist. 2021;26(1):7–16]. NRG1 fusion proteins provide an extracellular anchor for the epidermal growth factor (EGF) domain of NRG1 to bind to ErbB3 (HER3), leading to HER3 heterodimerization and activation of downstream signaling pathways, resulting in oncogenesis. Afatinib, an irreversible pan-ErbB tyrosine kinase inhibitor, represents a potential treatment for NRG1-fusion positive ( NRG1+) tumors. This study aims to examine the safety and efficacy of afatinib in patients with NRG1+ solid tumors, for which no authorized targeted therapy exists. Methods: This prospective, decentralized, US study (NCT05107193) will include 40 evaluable patients aged ≥18 years. Participating molecular test providers across the USA will identify eligible fusions in the course of routine diagnostic assays. When a patient with an NRG1 fusion is identified, participating test providers will notify the treating physician of the study as a treatment option for the patient. Patients’ primary oncologists will then contact the trial sponsor to confirm patient eligibility. Once approved by the central Institutional Review Board, patients will receive afatinib on a single-patient protocol basis, until disease progression or treatment is no longer tolerated. The recommended dosage per SmPC is 40 mg orally QD. Patients will be screened and enrolled into the study at their existing point-of-care setting. Inclusion criteria include a histologically or cytologically confirmed diagnosis of an advanced, unresectable/metastatic, non-hematologic malignancy with an NRG1 fusion, evaluable per RECIST 1.1. Any coding gene as the NRG1 fusion partner is permitted. Fusion status will be confirmed prospectively by a contracted molecular test provider. Exclusion criteria include prior systemic anti-cancer therapy or investigational drug within 14 days or 5 half-lives (whichever is shorter) of the start of afatinib treatment; an actionable driver mutation other than NRG1 fusion for which FDA-approved targeted therapy is available; and prior treatment with an ErbB-targeted therapy. The primary endpoint of the study is confirmed objective response (OR) by independent central review per RECIST 1.1, defined as best overall response of either complete response or partial response and analysed as the proportion of patients with an OR. The key secondary endpoint is duration of response, defined as the time from the first documented OR to progression or death. Secondary endpoints include time to OR and disease control per investigator assessment. Safety will also be assessed. The study is open for recruitment. Clinical trial information: NCT05107193.
Sclerokeratitis in Granulomatosis with Polyangiitis
Authors: Abigail Jebaraj, Amy Lin
Journal: New England Journal of Medicine (2022)

A 68-year-old man presented with a 2-month history of eye pain, redness, and blurry vision. He also had a 1-year history of dry cough, sinusitis, and unintentional weight loss. CT of the chest revealed lung nodules.
QOL-21. Language development and outcomes in pediatric brain tumor
Authors: Kelly Janke, Iris Paltin, Hannah Schofield, Megan Sy, Zoe Kearns
Journal: Neuro-Oncology (2022)

Abstract RATIONALE: Pediatric brain tumor (PBT) survivors are at risk for speech (e.g., articulation, prosody, fluency) and language (e.g., vocabulary, grammar, narratives, pragmatics) difficulties, though group outcomes vary with study design and individual risk factors (Hodges et al 2020). This study characterizes language functioning for clinically referred PBT survivors diagnosed in early childhood, a time of rapid language development and vulnerability. METHODS: Participants were 98 PBT patients (56 supratentorial) diagnosed by age 6 (M = 43.8 months, SD 24.4) who received tumor-directed intervention (surgery, chemotherapy, and/or radiation). Age at neuropsychological evaluation (2019 – 2022) was 2-19 years (M = 9.1, SD 4.1). Patients were 56% male, 73.5% White, and fluent English speakers. Verbal IQ, naming, working memory, fluency, comprehension, syntactic and phonological processing, and parent-reported functional communication outcomes were assessed. Rates of weak performance (1 SD&amp;lt;Mean) were compared to the expected base rate of 16%. RESULTS: Group means significantly diverged from age-expected performance in all domains except fluency. IQ correlated with most language measures, age at diagnosis (r .280, p .010), and time from diagnosis (r -.276, p .012). Weakness was identified on at least 1 verbal subtests for 71.4% of the full sample and most (57%) patients with IQ&amp;gt;84. Patients with NF1 (n=15) or treatment-related hearing concerns had lower reported functional communication. Naming difficulty was associated with supratentorial tumors; there were no other significant differences by tumor type or location. While functional communication correlated with several measures, weaknesses on performance-based and parent-report measures only corresponded for 44.6% of the sample. CONCLUSIONS: Language weaknesses are prevalent following early childhood PBT diagnosis. IQ and functional communication measures are useful indicators of risk, but more detailed and higher-level language measures are needed, particularly for cognitively intact patients. Additional implications and research needs will be discussed.
Trimodal therapy versus radical cystectomy for T2 bladder cancer: real-world evidence from Ontario
Authors: M.S. Wettstein, A. Berlin, S. Pham, S. Sridhar, P. Chung, A. Shabbir, T. Van Der Kwast, S.R. Qadri, K. Li, N. Liu, T. Hermanns, G.S. Kukarni
Journal: European Urology (2022)
Application of the KEYNOTE-564 trial results to real life population: Which patients with advanced kidney cancer should receive adjuvant pembrolizumab
Authors: G. Fallara, G. Rosiello, D. Raggi, L. Marandino, G. Malena, G. Basile, G. Colandrea, D. Cignoli, F. Belladelli, G. Musso, F. Cei, R. Bertini, A. Briganti, A. Salonia, F. Montorsi, A. Larcher, A. Necchi, U. Capitanio
Journal: European Urology (2022)